Developmental changes in nerve growth factor level in rat serum.

In serum, nerve growth factor (NGF) forms a complex with alpha 2-macroglobulin (alpha 2M), which formation inhibits the immunoreactivity between NGF and its antibodies. For measuring the serum level of NGF, it is thus necessary to liberate NGF from the NGF-alpha 2M complex and prevent reformation of such complex. The pretreatment of rat serum with 1 M guanidine hydrochloride for a few hours and operation of the enzyme immunoassay (EIA) in the presence of guanidine hydrochloride provided a reliable means for determination of the NGF level in serum. By this procedure we followed the serum NGF level in rats developmentally. It increased from prenatal day 2 to postnatal day 5 and decreased slightly at postnatal week 3, thereafter remaining constant throughout adulthood. In pregnant rats, the NGF level in serum increased threefold to fivefold before birth and then decreased rapidly. These data suggest that serum NGF level may reflect the demand for this molecule during establishment of the peripheral nervous system.     

Synthesis of Novel Aminopropylguanidine Derivatives with Potential Antihypertensive Activity

Pharmaceutical Research -     

Stepwise dissociation/denaturation and reassociation/renaturation of bovine α-crystallin in urea and guanidine hydrochloride: Sedimentation,fluorescence, near-ultraviolet and far-ultraviolet circular dichroism studies

Quaternary, tertiary and secondary structure changes of calf α-crystallin were studied as a function of urea and guanidine hydrochloride concentration at pH 7·3 and 20°C.Sedimentation velocity analysis shows that native α-crystallin (19 s, 850 000 M_r) dissociates in a step-wise fashion to single subunits (1·4 s, 20 000 M_r). Complete dissociation is reached above 5 m-urea or 2·5 m-guanidine hydrochloride. The most stable dissociation intermediate (12 s) is observed around 2–3 m-urea or 1–1·5 m-guanidine hydrochloride. Fluorescence and near-ultraviolet circular dichroism analyses indicate that the exposure of aromatic residues is correlated with step-wise dissociation. Far-ultraviolet circular dichroism analysis shows that unfolding of subunits occurs over a very wide range of denaturant concentrations. Unfolding begins as subunits are released from the 12 s dissociation intermediate and may not be complete even in 8 m-urea or 6 m-guanidine hydrochloride.Dissociation of native α-crystallin to 12 s intermediate is irreversible, but subsequent dissociation steps are reversible. Dissociated and denatured subunits can be reassembled in a 12 s ‘reassociated α-crystallin’ molecule which is identical to the 12 s dissociation intermediate in nearly every aspect of secondary, tertiary and quaternary structure.The results are discussed in relation to our earlier proposed three-layer subunit model of calf α-crystallin and are found to support this model.     

Synthesis and Biological Evaluation of Tricyclic Guanidine Analogues of Batzelladine K for Antimalarial,Antileishmanial, Antibacterial,Antifungal, and Anti‐HIV Activities

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV‐1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine‐sensitive D6 strain with IC₅₀ 1.25 and 0.88 μm and chloroquine‐resistant W2 strain with IC₅₀ 1.64 and 1.07 μm , respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC₅₀ 2.39 and 2.78 μm and IC₉₀ 11.27 and 12.76 μm , respectively. Three analogues 12c , 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC₅₀ < 3.02 μm and MIC/MBC/MFC <6 μm . Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV‐1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.     

甲氰咪胍治疗新生儿上消化道出血30例疗效观察

上消化道出血常是急性危重疾病的严重的合并症,处理不及时可危及生命.以上消化道出血为主要表现,我科应用甲氰咪胍治疗对30例新生儿进行治疗,效果满意.     

Exploring the Factors Affecting the Solubility of Chitosan in Water

We explore the role of crystallinity and inter‐ or intramolecular forces in chitosan for its solubility in water and demonstrate the expansion of its solubility to a wider pH range. Due to its semicrystalline nature, derived mainly from inter‐ and intramolecular hydrogen bonds, chitosan is water‐soluble only at pH < 6. In acidic conditions, its amino groups can be partially protonated resulting in repulsion between positively charged macrochains, thereby allowing diffusion of water molecules and subsequent solvation of macromolecules. We show that chemical disruption of chitosan crystallinity by partial re‐acetylation or physical disruption caused by the addition of urea and guanidine hydrochloride broadens the pH‐solubility range for this biopolymer.